Effect of physical activity and exercise on endometriosis-associated symptoms: a systematic review

Background: Endometriosis is a common benign gynecological disease that has the potential to debilitate due to pain and reduced quality of life. Treatment modalities such as hormones and surgery have limitations and do not treat all dimensions of the problems caused by endometriosis, and physical activity (PA) and exercise have been suggested as alternative treatments. Aim of this study was to perform a systematic review and meta-analysis to assess the effect of PA and exercise on endometriosis-associated symptoms.

Eleven databases were searched systematically. Study selection, quality assessment, and data extrac- tion were carried out by two independent researchers in accordance with PRISMA guidelines. Eligibility criteria were women with diagnosed endometriosis receiving an intervention (PA and/or exercise). The primary outcome was pain intensity, but all outcomes were accepted.

This study screened 1045 citations for eligibility. Four interventional studies were identified, of which one showed fatal design flaws and so was excluded. Three studies, two randomized controlled trials (RCT) and one pre- post study with no control group, involving 109 patients were included in a descriptive synthesis. The interventions included flexibility and strength training, cardiovascular fitness, and yoga, and were performed from one to four times per week for a total duration of 8–24 weeks, with or without supervision. Only one study found improvements in pain intensity. One study showed decreases in stress levels. Due to the heterogeneity of the study outcomes and measures, as well as confounding factors, a quantitative meta-analysis could not be performed.

The effect of PA and exercise as treatments for endometrioses-associated symptoms could not be determined due to significant limitations of the included studies. Future research should be based on RCTs of high methodological quality, measuring and reporting relevant core outcomes such as pain, improvements in symptoms and quality of life, and acceptability and satisfaction from the perspectives of patients. Furthermore, these outcomes need to be measured using reliable and validated tools. Trial registration number: CRD42021233138.

Physiotherapy, Pelvic pain, Endometriosis, Physical activity, Exercise, Quality of life © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Endometriosis is a benign gynecological condition in which ectopic, endometrium-like cells are located out - side of the uterine cavity [1 ]. The condition affects up to 10% of women of fertile age, with up to 70% being symptomatic [1 , 2]. The main clinical symptom of Open Access *Correspondence: [email protected] 1 School of Health Sciences, Kristiania University College, Prinsensgate 7-9, 0152 Oslo, Norway Full list of author information is available at the end of the article Page 2 of 10Tennfjord et al. BMC Women’s Health (2021) 21:355 endometriosis is severe pain during menstruation (dys - menorrhea) [1 ]. Pain during intercourse (dyspareunia) is also common, as well as the development of chronic pelvic pain (CPP) [1 , 2]. Other conditions associated with endometriosis include irritable bowel syndrome, painful bladder syndrome, abdominal pain, migraine, loss of quality of life and fatigue [2 – 4]. It is hypothe - sized that a specific immunological and inflammatory pathway is common to all of these conditions and endo - metriosis [3 , 5]. It takes a mean of 8 years to diagnose the endometriosis, during which musculoskeletal disor - ders secondary to endometriosis as well as psychologi - cal disorders may develop [6 , 7]. There is no definite cure for endometriosis, and so the main focus of management is to control the associ - ated pain, which is achieved by hormonal suppression of the disease or surgical excision [8]. Unfortunately, hormonal treatment can have intolerable side effects or become ineffective over time, while the effect of surgery is often short-lived [8]. Advances in the understanding of endometriosis have expanded the focus on less inva - sive and nonpharmacological treatments [8, 9]. Interna- tional clinical guidelines have suggested focusing on the role of physical activity (PA) and exercise as part of the therapeutic approach for women suffering from endo - metriosis-associated symptoms [10]. The inflammation that defines endometriosis causes sensitization of pelvic organs and, ultimately leading to CPP [11]. This mecha - nism makes it plausible for the anti-inflammatory effect of PA and exercise to impede the development of the dis- ease and ameliorate the associated pain [12]. PA and exercise were introduced for treating endome - triosis-associated symptoms more than 3  decades ago [13]. However, these interventions have been studied mostly in terms of their ability to reduce the risk of devel- oping endometriosis [12, 14, 15], and so little is known about the effect of PA and exercise on symptom improve- ment in women with endometriosis [12]. Some effect of PA and exercise has been found in women with CPP without endometriosis [16], but it is unclear whether this effect is transferable to women with endometriosis-asso - ciated pain [10]. Two previous systematic reviews have addressed the effect of PA and exercise on endometriosis-associated symptoms [17, 18]. However, these studies mainly focused on other complementary and alternative treat - ment options for endometriosis, such as mind–body interventions and acupuncture. The effect of PA and exercise specifically remained unclear since their searches were limited to a few databases, the search terms were not specified [18], or “PA” and “exercise” were not included as search terms [19]. This raises the possibil- ity that relevant studies on this subject were overlooked. The present systematic review attempted to identify interventional studies of high quality to assess the effect of PA and exercise specifically in treating women with endometriosis-associated symptoms. Review question What is the effect of PA and exercise on endometriosis- associated symptoms?

This systematic review was registered in the Inter - national Prospective Register of Systematic Reviews (CRD42021233138), and was performed in accordance with the PRISMA (Preferred Reporting Items for System- atic Reviews and Meta-Analyses) guidelines [20] (Addi - tional file 1). Eligibility criteria and search strategy Studies of interventions involving any type of PA and exercise were eligible for inclusion. PA was defined as “any bodily movement produced by skeletal muscles that requires energy expenditure” [21] and exercise was defined as “PA that is planned, structured, and repetitive for the purpose of conditioning the body” [21], consisting of cardiovascular conditioning, strength and resistance training, and flexibility. The study population consisted of women with any degree of endometriosis as diagnosed with an imaging or surgical modality, who presented with pain in the pelvic region (including dysmenorrhea, dyspareunia, or CPP). The primary outcome measure was the pain intensity, but all outcomes were accepted. Exclusion criteria were data presented in short com - munications, reviews, letters to the editor, and congress abstracts, and the application of passive interventions such as manual therapy to patients. The literature search was completed with support from a trained medical librarian. The search included the Cochrane Central Reg- ister of Controlled Trials, Embase, PubMed, MEDLINE, PsycInfo, CINAHL, AMED, Scopus, Web of Science, PEDro, and SveMed + , without time limitation up to December 2020. Publications could be in English, Swed - ish, Norwegian, Danish, or German. Search terms were identified through a pilot search for relevant literature. The electronic search strategy for this systematic review is presented in Additional file 2. In addition, the reference lists of included articles and identified reviews on the topic were scanned, and manually searched for further studies. Study selection and quality assessment In the first step, all obtained references were indepen - dently screened on the basis of the title and Abstract by Page 3 of 10 Tennfjord et al. BMC Women’s Health (2021) 21:355 M.K.T. and T.T. using the Rayyan web application [22] that allows blinded assessments. In the second step, all Abstracts with conflicting decisions were reviewed by both authors until consensus was reached. In the third step, the same authors independently assessed the meth - odological quality of the manuscripts that met the inclu - sion criteria, using quality assessment questionnaires appropriate for the design of each study as provided by the National Heart Lung and Blood Institute [23]. We applied the method of “quality assessment of controlled intervention studies” for randomized controlled trials (RCT), and the “quality assessment of before-after (pre- post) studies with no control group” for intervention studies with no control group while adding relevant ques- tions to determine exposure, risk, and confounding vari - ables. The assessment tools include several criteria rated “yes, ” “no, ” and “other: CD, cannot determine; NA, not applicable; NR, not reported. ” The quality of the included studies was rated as good, fair, or poor. We also used the Consensus on Exercise Reporting Template (CERT) [24], which is a 19-item checklist that yields a detailed descrip- tion of the minimum criteria that should be reported in an exercise intervention. The template provides indi - vidual scores for each included article (ranging from 0 to 19), in addition to a summary score for each item. Data extraction The full text of eligible articles was read by two reviewers (M.K.T. and T.T.), who independently extracted the fol - lowing data: author(s), year of publication, study period, country of origin, study design, sample size, inclusion and exclusion criteria, intervention type, description of intervention, follow-up period, primary and secondary outcomes, and dropout rate. Data reporting and summary measures A meta-analysis was planned, but it could not be per - formed due to the substantial heterogeneity found in study designs and outcomes. Results from the studies are reported as between- and within-group differences using mean ± standard-deviation values or numbers with per - centages, according to availability. Probability values were rounded to two decimal places, with the exception of p < 0.001. Confidence intervals were provided if available.

Study selection This study identified 1879 citations (Fig.  1). After removing duplicates, the remaining 1045 citations were screened for eligibility based on the title and Abstract. Seventeen publications were assessed for further inclu - sion reading the full-text versions of the articles, and four publications were included for quality assessment [25–28]. We identified four studies that described an intervention incorporating PA and/or exercise: two were RCTs [27, 28] and two were pre-post studies with no con- trol group [25, 26] (Tables 1, 2). Quality assessment, risk of bias, and exercise intervention assessment One study was rated as being of fair quality [27], while three were rated as poor quality [25, 26, 28]. The detailed assessment including signaling questions are presented in Tables 1 and 2. The RCT of Carpenter et al. [27] was judged as being of fair quality (Table  1). The main limi - tation of that RCT for the purpose of this review was that the participants were treated with danazol, which is a potent drug for treating endometriosis. Though hav - ing a control group, the study was underpowered for determining whether exercise had an additional effect to danazol. However, since the study was designed to inves - tigate if exercise could alleviate the side effects of dana - zol, it was not flawed per se. Moreover, the sample was too small to allow comparisons of individual side effects, important secondary outcomes (pelvic pain, dysmenor - rhea, and dyspareunia) were not reported, and the meth - ods of randomization and outcome assessment were not reported. The RCT of Goncalves et al. [28] was judged as being of poor quality due to significant differences in the base - line characteristics between the intervention and control groups (Table  1). The intervention group had a higher level of education, a high percentage of homemakers, and a lower rate of employment, which is a confounder for quality-of-life assessments. Also, one of the inclusion criteria was the presence of therapy-resistant CPP , which is a possible confounder for endometriosis-associated symptoms. Furthermore, the control group also received physiotherapy. Finally, the dropout rate in the interven - tion group was very high, at 30% (vs 0% in the control group). The study of Friggi Sebe Petrelluzzi et  al. [25] was judged as being of fair quality (Table  2). As in Goncalves et al. [28] only women with endometriosis and therapy- resistant CPP were included, representing a confounder. Furthermore, a sample-size calculation was not reported, and there was no control group. The intervention con - sisted not only of PA and exercise, but also a range of modalities including behavioral cognitive therapy, which confounds the contribution of PA and exercise to symp - tom improvement. The study of Awad et  al. [26] was judged as being of poor quality (Table  2). It was ultimately excluded from the synthesis since its design was fatally flawed by initi - ating medroxyprogesterone acetate, an effective hormo - nal treatment for endometriosis, at the same time as the Page 4 of 10Tennfjord et al. BMC Women’s Health (2021) 21:355 1 Records identified through database searching (n=1879) MEDLINE=171 PubMed=167 Embase=583 CINAHL=89 PsycInfo=13A MED=5C ochrane=316S copus=352 PEDro=14 SveMed+=14 Web of Science=155 ScreeningIncluded Eligibility Iden/g415fica/g415on Addi/g415onal records iden/g415fied from other sources (n=0) Recordsa /g332er duplicates removed (n=1045) Recordss creened (n=1045) Records excluded (n=1028) Full-text ar/g415cles assessed for eligibility (n=17) Full-text ar/g415cles excluded (n=13) Conference papers (n=7) Qualita/g415ve study( n=1) No interven/g415on (n=2) Study protocol (n=3) Studies included in descrip/g415ve analysis (n=3) Studies included in quan/g415ta/g415ve synthesis (meta-analysis) (n=0) Study excluded (n=1) Risk-of-bias assessment and interven/g415on assessment (CERT) (n=4) Fig. 1 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram for the identification, screening, eligibility, and inclusion of relevant articles Page 5 of 10 Tennfjord et al. BMC Women’s Health (2021) 21:355 intervention but without including a control group. Fur - thermore, no sample-size calculation was provided, and the inclusion and exclusion criteria appeared to be ran - dom from a clinical perspective. The individual scores for the articles based on the CERT checklist (Additional file  3) ranged from 7 to 14. None of the articles provided a description of exercise progression [25–28], and only one included a description of individually tailored exercises [27]. Exercise adherence was measured adequately in one study [27], as were moti- vational strategies [25]. The level of exercise was only described for two studies [27, 28]. Study populations The total study sample consisted of 109 participants [25, 27, 28] (Table  3). Two studies included women with surgically confirmed endometriosis [25, 27], while it was not specified how endometriosis was diagnosed by Goncalves et  al. [28]. The stage of endometriosis was not reported for any of the studies. The age of the included women was provided for two studies [25, 28]. All of the women in two studies [25, 28] also had CPP . Details of prior hormonal or surgical treatments were not provided for any of the studies. Table 1 Quality assessment of controlled intervention studies NA not applicable, NR not reported. The item “confounding variables measured and adjusted” was added to the original assessment form

Clearly stated study design Randomization adequate Treatment allocation concealed Participant and providers blinded Assessor blinded Baseline characteristics similar Dropout rate ≤ 20% Differential dropout rate ≤ 15% Goncalves et al. [28] Yes Yes Yes NA NA No No No Carpenter et al. [27] Yes Yes NR NA NR Yes Yes Yes

High adherence to treatment Other interventions Outcomes valid and reliable Sample size provided 80% power Predefined outcome measures Intention to treat Confounding variables measured and adjusted Quality rating (poor/fair/ good) Goncalves et al. [28] No No Yes Yes Yes Yes No Poor Carpenter et al. [27] Yes Yes Yes No Yes Yes No Fair Table 2 Quality assessment for before-after (pre-post) studies with no control group CD could not determine. Items “confounding variables measured and adjusted” and “exposure/risk defined/valid and reliable, and implemented consistently” was added to the original assessment form. *This study was excluded from the qualitative synthesis due to fatal flaws in its design

Question or

stated Eligible criteria pre-specified and described Participants representative of clinical population All eligible participants enrolled Sample size sufficient Intervention clearly described/ delivered consistently Outcomes prespecified /valid and reliable, and consistently implemented Blinded assessors Friggi Sebe Petrelluzzi et al. [25] Yes Yes Yes Yes CD Yes Yes NA Awad et al. [26] Yes Yes No No CD Yes Yes NA

Dropout rate ≤ 20% or accounted for in the analysis Statistics well described Outcomes tested multiple times Analysis of individual-level data Confounding variables measured and adjusted Exposure/risk defined/valid and reliable, and implemented consistently Quality rating (poor/fair/ good) Friggi Sebe Petrelluzzi et al. [25] Yes Yes no NA No Yes Poor Awad et al. [26] Yes Yes No NA No No Poor* Page 6 of 10Tennfjord et al. BMC Women’s Health (2021) 21:355 Table 3 Characteristics of the included studies 1 Confirmed by laparoscopy; 2mean ± standard deviation; 3not specified how diagnosed; NR not reported, QOL quality of life, RCT randomized controlled trial, PFM pelvic floor muscles, CPP chronic pelvic pain, VAS visual analogue scale, KINCOM Kinetic Communicator Exercise System, PSQ Perceived Stress Questionnaire, SF-36 36-item Short-Form Health Survey, EHP-30 Endometriosis Health Profile-30

Country Study period Study design Number Study population Intervention description Control group Duration Primary outcome (measure) Secondary outcomes (measure) Dropouts, n (%) Carpenter et al. [27] USA NR RCT 39 (18 inter- vention vs 18 controls) Endometriosis1 with no other hor- monal treatment during previous 12 months, no regular exercise Unsupervised; 40 min of individualized cardio fitness at 50–70% of max heart rate + flex- ibility exer- cises + danazol Danazol treat- ment only Four times weekly for 24 weeks Number of side effects of danazol (direct inquiry) Fitness (VO2max), general mus- cle strength (KINCOM), sex hormone levels, pelvic symptoms 3 (7.69%), only in control group Friggi Sebe Petrelluzzi et al. [25] Brazil NR Pre-post, no control group 30 Women with endometriosis1 and ≥ 7 years of CPP , with no effect of medical therapy or surgery, age 232.0 ± 1.30 years Supervised; 1 h of body aware- ness, breathing exercise, stretch- ing, general movement, PFM strength + 1.5 h behavioral cog- nitive therapy No control group 1.0 to 1.5 h for 10 weeks Pain (VAS, 0–10) Stress (PSQ), QOL (SF-36), salivary corti- sol levels 4 (13.33%) Goncalves et al. [28] Brazil 08/2013 to 12/2014 RCT 40 (28 inter- vention vs 12 controls) Endometriosis3 and CPP , prior hormonal and sur- gical therapy, age 234.88 ± 6.70 years, no regular exercise Supervised; 120 min of Hatha yoga, includ- ing posture (60 min) + con- versation (30 min) + relax- ation, breathing exercises, medi- tation (30 min) Medical therapy was continued Continu- ing medical therapy or physiotherapy once per week Twice weekly for 8 weeks QOL (EHP-30) Pain (VAS, 0–10), men- strual pattern measured daily (amount of bleeding scored from 0 to 5) 12 (30%), only in intervention group Page 7 of 10 Tennfjord et al. BMC Women’s Health (2021) 21:355 Interventions The performed interventions are listed in Table  1. No study performed a follow-up after the intervention had finished. Confounding interventions to PA and exercise were identified in all studies, as explained above. Limita - tions in the reporting of exercise interventions (according to the CERT) are also explained above. Primary and secondary outcome measures The primary and secondary outcomes for all studies are reported in Table 3. Only one study had “pain” as the pri- mary outcome [25]. The outcome reports were incom - plete for all studies. Effect of intervention on pain Goncalves et  al. [28] reported that the degree of daily pain was significantly lower in the intervention group than the control group, although the difference in the mean scores on a visual analogue scale (VAS) was not provided (p < 0.001). Furthermore, the scores in pain- related domains on Endometriosis Health Profile-30 (EHP-30) were significantly lower in the yoga group than the control group at postintervention (32.39 ± 21.95 ver- sus 55.05 ± 21.49, p < 0.001). Notably, the control group also received physiotherapy following the intervention at their institution. Friggi Sebe Petrelluzzi et al. [25] did not find a signifi - cant improvement in pain intensity (change in VAS score from pre- to posttreatment: 4.00 ± 0.56 to 3.30 ± 0.65, p > 0.05). Carpenter et al. [27] found that the pelvic pain decreased in both the intervention and control groups, with medical treatment using danazol providing no addi - tional effect relative to that obtained by PA and exercise. However, the exact results and significance level were not reported, leaving it uncertain about whether a type II error was present due to the sample being too small. Effects of intervention on mental health aspects and well-being The study of Friggi Sebe Petrelluzzi et al. [25] measured stress levels using the Perceived Stress Questionnaire (PSQ), salivary cortisol levels, and the 36-item Short- Form Health Survey (SF-36). The PSQ was developed as an outcome measure in psychosomatic research and was validated for use in Brazil [29]. Perceived stress was significantly lower at pretreatment (0.62 ± 0.02) than posttreatment (0.56 ± 0.02, p < 0.05). Significant improve- ments in the vitality and physical functioning domains of the SF-36 were also found (p < 0.05), but these effects were no longer significant after performing a multivariate analysis that included each variable in the SF-36. There was an overall decrease in salivary cortisol levels from pretreatment to posttreatment (p = 0.04), but this was not correlated with perceived stress as measured with PSQ. Goncalves et  al. [28] found significant improvements in certain EHP-30 items (control and powerlessness, emo - tional well-being, and self-image) in the intervention group compared with the control group (p < 0.001). Effect of intervention on pelvic floor dysfunction The study of Carpenter et  al. [27] assessed how exer - cise during danazol treatment could improve pelvic floor symptoms such as dyspareunia and dysmenorrhea. Those authors reported that the symptoms improved in both groups, but the values and significance levels were not provided. Goncalves et al. [28] found that the sexual- intercourse domain of EHP-30 was lower after 8 weeks of Hatha yoga in both the intervention and control groups, but the result did not reach between- or within-groups significance.

This systematic review has summarized the available evi - dence for the effect of PA and exercise on endometrio - sis-associated symptoms. We identified 4 interventional studies involving 129 women. However, 1 of these stud - ies was excluded after the quality assessment revealed fatal flaws in its design, leaving 109 women being finally included. Each included study found some improvement in pain intensity, stress levels, well-being, or self-image. However, due to confounding factors, the effect of PA and exercise alone could not be determined. Further - more, the heterogeneity of the outcome measures and incomplete outcome reporting made it impossible to conduct a quantitative meta-analysis. The relationship of PA and exercise with endometriosis has been widely studied in the past, and several reviews have been published on this topic [12, 14, 15, 18, 19]. However, their results have been inconclusive, mainly due to inclusion of observational studies of how PA and exercise may lower the risk of developing endometriosis [12, 14, 15]. Another possible reason for the inconclu - sive findings is the diversity in the type of interventions included in other systematic reviews [18, 19], where the focus has spanned from acupuncture and yoga to electro- therapy and exercise. A multimodal approach that includes physiotherapy has been suggested to alleviate endometriosis symptoms [10, 30, 31]. Physiotherapy contains both active and pas - sive modalities, but the optimal physiotherapy approach for endometriosis-associated symptoms is not clear [16]. The theory supporting PA and exercise as a ben - eficial approach involves viewing the skeletal muscles as an endocrine organ, with contraction of these muscles releasing myokines [32]. These myokines may exert direct effects on the muscle itself or distal organs such as the Page 8 of 10Tennfjord et al. BMC Women’s Health (2021) 21:355 liver, pancreas, or adipose tissue [32]. Furthermore, exer - cise increases the production of leucocytes, cortisol, and adrenaline, all of which have potent acute anti‐inflamma- tory effects [33]. The present review specifically focused on PA and exer- cise, but it was not possible to summarize the effect due to significant limitations of the included studies. How - ever, some trends could be identified. One study showed improvements in daily pain scores [28], but no effect-size measures were provided, and so the strength of this asso - ciation was uncertain. Furthermore, the effect of Hatha yoga was questionable due to the additional time spent on relaxation and meditation [28]. A recent systematic review and meta-analysis produced evidence that medi - tation itself is effective in improving the quality of life and pain in women with CPP [34], which was an inclu - sion criterion in the present study. However, the two other studies in our review did not find an effect from PA and exercise on pain [25, 27]. No sample-size calcula- tions were performed for those two studies, and so type II errors might have been present. There seems to be a dose–response relationship between regular, high-intensity exercise and the effect on the inflammatory profile in general [33]. Since none of the studies in this review included descriptions of exer - cise progression [25, 27, 28] (Additional file  3), we can only speculate if the effect of PA and exercise would have been stronger if progressive overload had been achieved [24]. Other reported effects were reduced stress levels by Friggi Sebe Petrelluzzi et  al. [25], and improvements in well-being and body image by Goncalves et al. [28]. Both of these studies included women with CPP and applied a cognitive approach in addition to PA and exercise, which are both possible confounders for the effect of PA and exercise on endometriosis-associated symptoms [34]. Previous research has found that the pelvic floor mus - cle tension in higher in women suffering from endome - triosis pain [35] than in controls without endometriosis. Since a large proportion of women with endometriosis suffer from dyspareunia and CPP [1, 2], it is surpris - ing that only one of the present studies investigated the pelvic floor muscles [25]; however, pain scores specifi - cally for the pelvic floor or measurements of the pelvic floor muscles were not reported. Lastly, none of the stud- ies measured patient satisfaction. The high dropout rate found by Goncalves et  al. [28] indicates that it is perti - nent to design exercise interventions that meet the needs of patients and fit their lifestyle. In a recent initiative, healthcare professionals and women suffering from endometriosis were able to rec - ommend a minimum set of outcomes to be meas - ured and reported in all interventional clinical trials of endometriosis [36]. Those so-called core outcomes aim to focus research on meaningful endpoints for the users of health services [37]. Patient satisfaction with the treat - ment was one of those outcomes. There are several ongo- ing RCTs related to PA and exercise [38–40] that are measuring the following core items: pain, improvement in symptoms and quality of life, patient acceptability, and patient satisfaction with the treatment. These trials might yield evidence-based advice on PA and exercise for women with endometriosis-associated symptoms in the future. Strength and limitations The strengths of this systematic review include its origi - nality, rigorous search strategy, and methodological robustness. Its main limitation is the low grade of evi - dence that could be obtained from the previous studies. The small samples, confounding factors, heterogeneity of interventions, and poor reporting of details about the exercise intervention and outcome measures restricts our ability to draw overall conclusions about the effect of PA and exercise in treating endometriosis-associated symptoms.

PA and exercise might exert a range of beneficial effects on endometriosis-associated symptoms, but unfor - tunately these effects cannot be robustly determined based on the existing literature. Nevertheless, the poten - tially beneficial role of PA and exercise should be com - municated to women with endometriosis-associated symptoms. Future research should be based on RCTs of high methodological quality, measuring and reporting relevant core outcomes such as pain, improvements in symptoms and quality of life, and acceptability and sat - isfaction from the perspectives of patients. Furthermore, these outcomes need to be measured using reliable and validated tools. A focus on the type and dose of PA and exercise as well as patient selection is warranted, and using appropriate checklists such as the CERT is recom - mended. Since endometriosis patients can show complex symptomatology, the cooperation of multiple disciplines such as physiotherapists and gynecologists could improve the quality of clinical research in this field. Abbreviations PA: Physical activity; RCT : Randomized controlled trials; CPP: Chronic pelvic pain; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta- Analyses; CERT: Consensus on Exercise Reporting Template; VAS: Visual ana- logue scale; EHP-30: Endometriosis Health Profile-30; P: P-value; PSQ: Perceived Stress Questionnaire; SF-36: 36-Item Short-Form Health Survey. Page 9 of 10 Tennfjord et al. BMC Women’s Health (2021) 21:355 Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1186/ s12905- 021- 01500-4. Additional file 1. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Additional file 2. Electronic search strategy with search terms. Additional file 3. CERT (Consensus on Exercise Reporting Template).

We would like to show our sincere gratitude towards our librarian Åse Marit Hammersbøen that performed the systematic search. Authors’ contributions MKT planned the study, identified and screened for relevant papers, per- formed the quality assessment, wrote the manuscript and had the overall responsibility of its content and text. RG: planned the study and took part in the identification and screening of relevant papers and wrote the manuscript. TT: planned the study, identified and screened for relevant papers, performed the quality assessment and wrote the manuscript. All authors read and approved the final manuscript. Funding This research did not receive any specific funding from agencies in the public, commercial, or not-for-profit sectors. Availability of data and materials Not applicable. Relevant material is attached as Additional files. Declarations Ethics approval and consent to participate Ethical approval was not required due to the design of this study. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Author details 1 School of Health Sciences, Kristiania University College, Prinsensgate 7-9, 0152 Oslo, Norway. 2 Department of Obstetrics and Gynecology, Akershus University Hospital, Sykehusveien 25, 1478 Nordbyhagen, Norway. 3 Tollbugata Fysioterapi, Tollbugata 13, 3044 Drammen, Norway. 4 Department of Gynecol- ogy, Oslo University Hospital, PB 0424, 0459 Nydalen, Oslo, Norway. Received: 4 May 2021 Accepted: 27 September 2021

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